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FDA expands approval of obinutuzumab
The US Food and Drug Administration (FDA) has expanded the approved use of obinutuzumab (Gazyva®).
The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated follicular lymphoma (FL) that is advanced (stage II bulky, stage III, or stage IV) .
In patients who respond to this treatment, obinutuzumab monotherapy can be given as maintenance.
The FDA granted this new approval of obinutuzumab to Genentech, Inc. The application for obinutuzumab in this indication received priority review.
The latest FDA approval means obinutuzumab is available in the US for the following indications:
- In combination with chlorambucil to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment
- In combination with bendamustine, followed by obinutuzumab alone, to treat FL in adults who did not respond to a rituximab-containing regimen or whose FL returned after such treatment
- In combination with chemotherapy, followed by obinutuzumab alone in responders, to treat stage II bulky, stage III, or stage IV FL in adults who have not had previous FL treatment.
Phase 3 results
The latest approval of obinutuzumab is based on results from the phase 3 GALLIUM study, which were presented at the 2016 ASH Annual Meeting and published in NEJM in October.
The following are updated data from the obinutuzumab prescribing information.
GALLIUM included 1385 patients with previously untreated non-Hodgkin lymphoma, and 1202 of these patients had advanced FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.
At a median observation time of 38 months, the overall response rate was 91% in the obinutuzumab arm and 88% in the rituximab arm. The complete response rates were 28% and 27%, respectively.
The median progression-free survival was not reached in either arm. The hazard ratio, for obinutuzumab compared to rituximab, was 0.72 (95% CI, 0.56-0.93, P=0.0118).
Safety was evaluated based on all 1385 patients in the study, 86% of whom had previously untreated FL and 14% of whom had marginal zone lymphoma.
Serious adverse events (AEs) occurred in 50% of patients in the obinutuzumab arm and 43% in the rituximab arm. Fatal AEs occurred in 5% and 4%, respectively. Infections and second malignancies were the leading causes of these deaths.
The most common AEs (incidence ≥ 20%) observed at least 2% more patients in the obinutuzumab arm were infusion-related reactions, neutropenia, upper respiratory tract infection, cough, constipation, and diarrhea.
The most common grade 3 to 5 AEs (incidence ≥ 5%) observed more frequently in the obinutuzumab arm were neutropenia, infusion-related reactions, febrile neutropenia, and thrombocytopenia. 
The US Food and Drug Administration (FDA) has expanded the approved use of obinutuzumab (Gazyva®).
The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated follicular lymphoma (FL) that is advanced (stage II bulky, stage III, or stage IV) .
In patients who respond to this treatment, obinutuzumab monotherapy can be given as maintenance.
The FDA granted this new approval of obinutuzumab to Genentech, Inc. The application for obinutuzumab in this indication received priority review.
The latest FDA approval means obinutuzumab is available in the US for the following indications:
- In combination with chlorambucil to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment
- In combination with bendamustine, followed by obinutuzumab alone, to treat FL in adults who did not respond to a rituximab-containing regimen or whose FL returned after such treatment
- In combination with chemotherapy, followed by obinutuzumab alone in responders, to treat stage II bulky, stage III, or stage IV FL in adults who have not had previous FL treatment.
Phase 3 results
The latest approval of obinutuzumab is based on results from the phase 3 GALLIUM study, which were presented at the 2016 ASH Annual Meeting and published in NEJM in October.
The following are updated data from the obinutuzumab prescribing information.
GALLIUM included 1385 patients with previously untreated non-Hodgkin lymphoma, and 1202 of these patients had advanced FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.
At a median observation time of 38 months, the overall response rate was 91% in the obinutuzumab arm and 88% in the rituximab arm. The complete response rates were 28% and 27%, respectively.
The median progression-free survival was not reached in either arm. The hazard ratio, for obinutuzumab compared to rituximab, was 0.72 (95% CI, 0.56-0.93, P=0.0118).
Safety was evaluated based on all 1385 patients in the study, 86% of whom had previously untreated FL and 14% of whom had marginal zone lymphoma.
Serious adverse events (AEs) occurred in 50% of patients in the obinutuzumab arm and 43% in the rituximab arm. Fatal AEs occurred in 5% and 4%, respectively. Infections and second malignancies were the leading causes of these deaths.
The most common AEs (incidence ≥ 20%) observed at least 2% more patients in the obinutuzumab arm were infusion-related reactions, neutropenia, upper respiratory tract infection, cough, constipation, and diarrhea.
The most common grade 3 to 5 AEs (incidence ≥ 5%) observed more frequently in the obinutuzumab arm were neutropenia, infusion-related reactions, febrile neutropenia, and thrombocytopenia.
The US Food and Drug Administration (FDA) has expanded the approved use of obinutuzumab (Gazyva®).
The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated follicular lymphoma (FL) that is advanced (stage II bulky, stage III, or stage IV) .
In patients who respond to this treatment, obinutuzumab monotherapy can be given as maintenance.
The FDA granted this new approval of obinutuzumab to Genentech, Inc. The application for obinutuzumab in this indication received priority review.
The latest FDA approval means obinutuzumab is available in the US for the following indications:
- In combination with chlorambucil to treat chronic lymphocytic leukemia (CLL) in adults who have not had previous CLL treatment
- In combination with bendamustine, followed by obinutuzumab alone, to treat FL in adults who did not respond to a rituximab-containing regimen or whose FL returned after such treatment
- In combination with chemotherapy, followed by obinutuzumab alone in responders, to treat stage II bulky, stage III, or stage IV FL in adults who have not had previous FL treatment.
Phase 3 results
The latest approval of obinutuzumab is based on results from the phase 3 GALLIUM study, which were presented at the 2016 ASH Annual Meeting and published in NEJM in October.
The following are updated data from the obinutuzumab prescribing information.
GALLIUM included 1385 patients with previously untreated non-Hodgkin lymphoma, and 1202 of these patients had advanced FL.
Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).
The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.
At a median observation time of 38 months, the overall response rate was 91% in the obinutuzumab arm and 88% in the rituximab arm. The complete response rates were 28% and 27%, respectively.
The median progression-free survival was not reached in either arm. The hazard ratio, for obinutuzumab compared to rituximab, was 0.72 (95% CI, 0.56-0.93, P=0.0118).
Safety was evaluated based on all 1385 patients in the study, 86% of whom had previously untreated FL and 14% of whom had marginal zone lymphoma.
Serious adverse events (AEs) occurred in 50% of patients in the obinutuzumab arm and 43% in the rituximab arm. Fatal AEs occurred in 5% and 4%, respectively. Infections and second malignancies were the leading causes of these deaths.
The most common AEs (incidence ≥ 20%) observed at least 2% more patients in the obinutuzumab arm were infusion-related reactions, neutropenia, upper respiratory tract infection, cough, constipation, and diarrhea.
The most common grade 3 to 5 AEs (incidence ≥ 5%) observed more frequently in the obinutuzumab arm were neutropenia, infusion-related reactions, febrile neutropenia, and thrombocytopenia.
CAR T-cell therapy on fast track with FDA, EMA
A chimeric antigen receptor (CAR) T-cell therapy, bb2121, has received breakthrough therapy designation from the US Food and Drug Administration (FDA) and was granted access to the European Medicines Agency’s (EMA’s) PRIority MEdicines (PRIME) program.
The CAR T-cell therapy is designed to target B-cell maturation antigen in previously treated patients with multiple myeloma.
bb2121 is being developed by bluebird bio, Inc., and Celgene Corporation.
The EMA’s and FDA’s decisions on bb2121 were based on preliminary data from an ongoing phase 1 study, CRB-401 (NCT02658929).
Results from this study were presented at the 2017 ASCO Annual Meeting (abstract 3010).
The study enrolled patients with relapsed and/or refractory multiple myeloma. As of the May 4, 2017 data cut-off, 21 patients had been enrolled.
Patients had a median of 7 prior lines of therapy (range, 3-14). Their previous treatments included lenalidomide and bortezomib (100%), pomalidomide and carfilzomib (91%), daratumumab (71%), and autologous stem cell transplant (100% at least once).
Twenty-nine percent of patients were refractory to bortezomib, lenalidomide, carfilzomib, pomalidomide, and daratumumab.
Patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by an infusion of bb2121 at 1 of 4 doses: 50 x 106, 150 x 106, 450 x 106 and 800 x 106 CAR+ T cells.
All 21 patients were evaluable for safety.
The most common treatment-emergent grade 3-4 adverse events were cytopenias commonly associated with the lymphodepletion regimen, as well as grade 3 events of hyponatremia (n=4), upper respiratory infection (n=2), syncope (n=2), and cytokine release syndrome (CRS, n=2).
In all, 71% of patients (15/21) had CRS, mostly grade 1 and 2. For the 2 patients with grade 3 CRS, it resolved within 24 hours. To manage CRS, 4 patients received tocilizumab, and 1 (with grade 2) received steroids as well.
Eighteen patients were evaluable for efficacy, and the overall response rate was 89% (16/18).
There were 4 complete responses—2 in the 150 x 106 cohort, 1 in the 450 x 106 cohort, and 1 in the 800 x 106 cohort. The complete responder in the 450 x 106 cohort ultimately died of cardiopulmonary arrest that was deemed unrelated to treatment.
Five patients had a partial response—2 in the 450 x 106 cohort and 1 in each of the other cohorts. Seven patients had a very good partial response—5 in the 450 x 106 cohort and 1 each in the 150 x 106 cohort and 800 x 106 cohort.
Updated data from this study are scheduled to be presented at the 2017 ASH Annual Meeting (abstract 740).
About breakthrough designation
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
About PRIME
The EMA launched its PRIME program to enhance support for the development of medicines that target an unmet medical need.
The program involves enhanced interaction and early dialogue with developers of promising medicines to optimize development plans and speed up evaluation so these medicines can reach patients earlier.
PRIME focuses on medicines that may offer a major therapeutic advantage over existing treatments or benefit patients without treatment options. To be accepted for PRIME, a medicine must have demonstrated the potential to benefit patients with unmet medical needs based on early clinical data.
A chimeric antigen receptor (CAR) T-cell therapy, bb2121, has received breakthrough therapy designation from the US Food and Drug Administration (FDA) and was granted access to the European Medicines Agency’s (EMA’s) PRIority MEdicines (PRIME) program.
The CAR T-cell therapy is designed to target B-cell maturation antigen in previously treated patients with multiple myeloma.
bb2121 is being developed by bluebird bio, Inc., and Celgene Corporation.
The EMA’s and FDA’s decisions on bb2121 were based on preliminary data from an ongoing phase 1 study, CRB-401 (NCT02658929).
Results from this study were presented at the 2017 ASCO Annual Meeting (abstract 3010).
The study enrolled patients with relapsed and/or refractory multiple myeloma. As of the May 4, 2017 data cut-off, 21 patients had been enrolled.
Patients had a median of 7 prior lines of therapy (range, 3-14). Their previous treatments included lenalidomide and bortezomib (100%), pomalidomide and carfilzomib (91%), daratumumab (71%), and autologous stem cell transplant (100% at least once).
Twenty-nine percent of patients were refractory to bortezomib, lenalidomide, carfilzomib, pomalidomide, and daratumumab.
Patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by an infusion of bb2121 at 1 of 4 doses: 50 x 106, 150 x 106, 450 x 106 and 800 x 106 CAR+ T cells.
All 21 patients were evaluable for safety.
The most common treatment-emergent grade 3-4 adverse events were cytopenias commonly associated with the lymphodepletion regimen, as well as grade 3 events of hyponatremia (n=4), upper respiratory infection (n=2), syncope (n=2), and cytokine release syndrome (CRS, n=2).
In all, 71% of patients (15/21) had CRS, mostly grade 1 and 2. For the 2 patients with grade 3 CRS, it resolved within 24 hours. To manage CRS, 4 patients received tocilizumab, and 1 (with grade 2) received steroids as well.
Eighteen patients were evaluable for efficacy, and the overall response rate was 89% (16/18).
There were 4 complete responses—2 in the 150 x 106 cohort, 1 in the 450 x 106 cohort, and 1 in the 800 x 106 cohort. The complete responder in the 450 x 106 cohort ultimately died of cardiopulmonary arrest that was deemed unrelated to treatment.
Five patients had a partial response—2 in the 450 x 106 cohort and 1 in each of the other cohorts. Seven patients had a very good partial response—5 in the 450 x 106 cohort and 1 each in the 150 x 106 cohort and 800 x 106 cohort.
Updated data from this study are scheduled to be presented at the 2017 ASH Annual Meeting (abstract 740).
About breakthrough designation
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
About PRIME
The EMA launched its PRIME program to enhance support for the development of medicines that target an unmet medical need.
The program involves enhanced interaction and early dialogue with developers of promising medicines to optimize development plans and speed up evaluation so these medicines can reach patients earlier.
PRIME focuses on medicines that may offer a major therapeutic advantage over existing treatments or benefit patients without treatment options. To be accepted for PRIME, a medicine must have demonstrated the potential to benefit patients with unmet medical needs based on early clinical data.
A chimeric antigen receptor (CAR) T-cell therapy, bb2121, has received breakthrough therapy designation from the US Food and Drug Administration (FDA) and was granted access to the European Medicines Agency’s (EMA’s) PRIority MEdicines (PRIME) program.
The CAR T-cell therapy is designed to target B-cell maturation antigen in previously treated patients with multiple myeloma.
bb2121 is being developed by bluebird bio, Inc., and Celgene Corporation.
The EMA’s and FDA’s decisions on bb2121 were based on preliminary data from an ongoing phase 1 study, CRB-401 (NCT02658929).
Results from this study were presented at the 2017 ASCO Annual Meeting (abstract 3010).
The study enrolled patients with relapsed and/or refractory multiple myeloma. As of the May 4, 2017 data cut-off, 21 patients had been enrolled.
Patients had a median of 7 prior lines of therapy (range, 3-14). Their previous treatments included lenalidomide and bortezomib (100%), pomalidomide and carfilzomib (91%), daratumumab (71%), and autologous stem cell transplant (100% at least once).
Twenty-nine percent of patients were refractory to bortezomib, lenalidomide, carfilzomib, pomalidomide, and daratumumab.
Patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by an infusion of bb2121 at 1 of 4 doses: 50 x 106, 150 x 106, 450 x 106 and 800 x 106 CAR+ T cells.
All 21 patients were evaluable for safety.
The most common treatment-emergent grade 3-4 adverse events were cytopenias commonly associated with the lymphodepletion regimen, as well as grade 3 events of hyponatremia (n=4), upper respiratory infection (n=2), syncope (n=2), and cytokine release syndrome (CRS, n=2).
In all, 71% of patients (15/21) had CRS, mostly grade 1 and 2. For the 2 patients with grade 3 CRS, it resolved within 24 hours. To manage CRS, 4 patients received tocilizumab, and 1 (with grade 2) received steroids as well.
Eighteen patients were evaluable for efficacy, and the overall response rate was 89% (16/18).
There were 4 complete responses—2 in the 150 x 106 cohort, 1 in the 450 x 106 cohort, and 1 in the 800 x 106 cohort. The complete responder in the 450 x 106 cohort ultimately died of cardiopulmonary arrest that was deemed unrelated to treatment.
Five patients had a partial response—2 in the 450 x 106 cohort and 1 in each of the other cohorts. Seven patients had a very good partial response—5 in the 450 x 106 cohort and 1 each in the 150 x 106 cohort and 800 x 106 cohort.
Updated data from this study are scheduled to be presented at the 2017 ASH Annual Meeting (abstract 740).
About breakthrough designation
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
About PRIME
The EMA launched its PRIME program to enhance support for the development of medicines that target an unmet medical need.
The program involves enhanced interaction and early dialogue with developers of promising medicines to optimize development plans and speed up evaluation so these medicines can reach patients earlier.
PRIME focuses on medicines that may offer a major therapeutic advantage over existing treatments or benefit patients without treatment options. To be accepted for PRIME, a medicine must have demonstrated the potential to benefit patients with unmet medical needs based on early clinical data.
Rigosertib produces better OS in MDS than tAML
Rigosertib has demonstrated activity and tolerability in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia transformed from MDS (tAML), according to researchers.
In a phase 1/2 study, rigosertib produced responses in a quarter of MDS/tAML patients and enabled stable disease in another quarter.
Overall survival (OS) was about a year longer for responders than for non-responders.
MDS patients were more likely to respond to rigosertib and therefore enjoyed longer OS than tAML patients.
Overall, rigosertib was considered well-tolerated. There were no treatment-related deaths, though 18% of patients experienced treatment-related serious adverse events (AEs).
Lewis Silverman, MD, of Icahn School of Medicine at Mount Sinai in New York, New York, and his colleagues described these results in Leukemia Research.
The study was sponsored by Onconova Therapeutics, Inc., the company developing rigosertib.
Rigosertib is an inhibitor of Ras-effector pathways that interacts with the Ras binding domains common to several signaling proteins, including Raf and PI3 kinase.
Dr Silverman and his colleagues tested intravenous rigosertib in a dose-escalation, phase 1/2 study of 22 patients. Patients had tAML (n=13), high-risk MDS (n=6), intermediate-2-risk MDS (n=2), or chronic myelomonocytic leukemia (n=1).
All patients had relapsed or were refractory to standard therapy and had no approved options for second-line therapies. The patients’ median age was 78 (range, 59-84), and 90% were male.
Patients received 3- to 7-day continuous infusions of rigosertib at doses ranging from 650 mg/m2/day to 1700 mg/m2/day in 14-day cycles.
The mean number of treatment cycles was 5.6 ± 5.8 (range, 1-23). The maximum tolerated dose of rigosertib was 1700 mg/m2/day, and the recommended phase 2 dose was 1375 mg/m2/day.
Safety
All patients had at least 1 AE. The most common AEs of any grade were fatigue (n=16, 73%), diarrhea (n=12, 55%), pyrexia (n=12, 55%), dyspnea (n=11, 50%), insomnia (n=11, 50%), anemia (n=10, 46%), constipation (n=9, 41%), nausea (n=9, 41%), cough (n=9, 41%), and decreased appetite (n=9, 41%).
The most common grade 3 or higher AEs were anemia (n=9, 41%), thrombocytopenia (n=5, 23%), pneumonia (n=5, 23%), hypoglycemia (n=4, 18%), hyponatremia (n=4, 18%), and hypophosphatemia (n=4, 18%).
Four patients (18%) had treatment-related serious AEs. This included hematuria and pollakiuria (n=1), dysuria and pollakiuria (n=1), asthenia (n=1), and dyspnea (n=1). Thirteen patients (59%) stopped treatment due to AEs.
Ten patients, who remained on study from 1 to 19 months, died within 30 days of stopping rigosertib. There were no treatment-related deaths.
Efficacy
Nineteen patients were evaluable for efficacy.
Five patients responded to treatment. Four patients with MDS had a marrow complete response, and 1 with tAML had a marrow partial response. Two of the patients with marrow complete response also had hematologic improvements.
Five patients had stable disease, 3 with MDS and 2 with tAML.
The median OS was 15.7 months for responders and 2.0 months for non-responders (P=0.0070). The median OS was 12.0 months for MDS patients and 2.0 months for tAML patients (P<0.0001).
“The publication of results from this historical study provides support of the relationship between bone marrow blast response and improvement in overall survival in this group of patients with MDS and acute myeloid leukemia for whom no FDA-approved treatments are currently available,” said Ramesh Kumar, president and chief executive officer of Onconova Therapeutics, Inc.
He added that these data are “fundamental to the rationale” of ongoing studies of rigosertib in high-risk MDS patients.
Rigosertib has demonstrated activity and tolerability in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia transformed from MDS (tAML), according to researchers.
In a phase 1/2 study, rigosertib produced responses in a quarter of MDS/tAML patients and enabled stable disease in another quarter.
Overall survival (OS) was about a year longer for responders than for non-responders.
MDS patients were more likely to respond to rigosertib and therefore enjoyed longer OS than tAML patients.
Overall, rigosertib was considered well-tolerated. There were no treatment-related deaths, though 18% of patients experienced treatment-related serious adverse events (AEs).
Lewis Silverman, MD, of Icahn School of Medicine at Mount Sinai in New York, New York, and his colleagues described these results in Leukemia Research.
The study was sponsored by Onconova Therapeutics, Inc., the company developing rigosertib.
Rigosertib is an inhibitor of Ras-effector pathways that interacts with the Ras binding domains common to several signaling proteins, including Raf and PI3 kinase.
Dr Silverman and his colleagues tested intravenous rigosertib in a dose-escalation, phase 1/2 study of 22 patients. Patients had tAML (n=13), high-risk MDS (n=6), intermediate-2-risk MDS (n=2), or chronic myelomonocytic leukemia (n=1).
All patients had relapsed or were refractory to standard therapy and had no approved options for second-line therapies. The patients’ median age was 78 (range, 59-84), and 90% were male.
Patients received 3- to 7-day continuous infusions of rigosertib at doses ranging from 650 mg/m2/day to 1700 mg/m2/day in 14-day cycles.
The mean number of treatment cycles was 5.6 ± 5.8 (range, 1-23). The maximum tolerated dose of rigosertib was 1700 mg/m2/day, and the recommended phase 2 dose was 1375 mg/m2/day.
Safety
All patients had at least 1 AE. The most common AEs of any grade were fatigue (n=16, 73%), diarrhea (n=12, 55%), pyrexia (n=12, 55%), dyspnea (n=11, 50%), insomnia (n=11, 50%), anemia (n=10, 46%), constipation (n=9, 41%), nausea (n=9, 41%), cough (n=9, 41%), and decreased appetite (n=9, 41%).
The most common grade 3 or higher AEs were anemia (n=9, 41%), thrombocytopenia (n=5, 23%), pneumonia (n=5, 23%), hypoglycemia (n=4, 18%), hyponatremia (n=4, 18%), and hypophosphatemia (n=4, 18%).
Four patients (18%) had treatment-related serious AEs. This included hematuria and pollakiuria (n=1), dysuria and pollakiuria (n=1), asthenia (n=1), and dyspnea (n=1). Thirteen patients (59%) stopped treatment due to AEs.
Ten patients, who remained on study from 1 to 19 months, died within 30 days of stopping rigosertib. There were no treatment-related deaths.
Efficacy
Nineteen patients were evaluable for efficacy.
Five patients responded to treatment. Four patients with MDS had a marrow complete response, and 1 with tAML had a marrow partial response. Two of the patients with marrow complete response also had hematologic improvements.
Five patients had stable disease, 3 with MDS and 2 with tAML.
The median OS was 15.7 months for responders and 2.0 months for non-responders (P=0.0070). The median OS was 12.0 months for MDS patients and 2.0 months for tAML patients (P<0.0001).
“The publication of results from this historical study provides support of the relationship between bone marrow blast response and improvement in overall survival in this group of patients with MDS and acute myeloid leukemia for whom no FDA-approved treatments are currently available,” said Ramesh Kumar, president and chief executive officer of Onconova Therapeutics, Inc.
He added that these data are “fundamental to the rationale” of ongoing studies of rigosertib in high-risk MDS patients.
Rigosertib has demonstrated activity and tolerability in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia transformed from MDS (tAML), according to researchers.
In a phase 1/2 study, rigosertib produced responses in a quarter of MDS/tAML patients and enabled stable disease in another quarter.
Overall survival (OS) was about a year longer for responders than for non-responders.
MDS patients were more likely to respond to rigosertib and therefore enjoyed longer OS than tAML patients.
Overall, rigosertib was considered well-tolerated. There were no treatment-related deaths, though 18% of patients experienced treatment-related serious adverse events (AEs).
Lewis Silverman, MD, of Icahn School of Medicine at Mount Sinai in New York, New York, and his colleagues described these results in Leukemia Research.
The study was sponsored by Onconova Therapeutics, Inc., the company developing rigosertib.
Rigosertib is an inhibitor of Ras-effector pathways that interacts with the Ras binding domains common to several signaling proteins, including Raf and PI3 kinase.
Dr Silverman and his colleagues tested intravenous rigosertib in a dose-escalation, phase 1/2 study of 22 patients. Patients had tAML (n=13), high-risk MDS (n=6), intermediate-2-risk MDS (n=2), or chronic myelomonocytic leukemia (n=1).
All patients had relapsed or were refractory to standard therapy and had no approved options for second-line therapies. The patients’ median age was 78 (range, 59-84), and 90% were male.
Patients received 3- to 7-day continuous infusions of rigosertib at doses ranging from 650 mg/m2/day to 1700 mg/m2/day in 14-day cycles.
The mean number of treatment cycles was 5.6 ± 5.8 (range, 1-23). The maximum tolerated dose of rigosertib was 1700 mg/m2/day, and the recommended phase 2 dose was 1375 mg/m2/day.
Safety
All patients had at least 1 AE. The most common AEs of any grade were fatigue (n=16, 73%), diarrhea (n=12, 55%), pyrexia (n=12, 55%), dyspnea (n=11, 50%), insomnia (n=11, 50%), anemia (n=10, 46%), constipation (n=9, 41%), nausea (n=9, 41%), cough (n=9, 41%), and decreased appetite (n=9, 41%).
The most common grade 3 or higher AEs were anemia (n=9, 41%), thrombocytopenia (n=5, 23%), pneumonia (n=5, 23%), hypoglycemia (n=4, 18%), hyponatremia (n=4, 18%), and hypophosphatemia (n=4, 18%).
Four patients (18%) had treatment-related serious AEs. This included hematuria and pollakiuria (n=1), dysuria and pollakiuria (n=1), asthenia (n=1), and dyspnea (n=1). Thirteen patients (59%) stopped treatment due to AEs.
Ten patients, who remained on study from 1 to 19 months, died within 30 days of stopping rigosertib. There were no treatment-related deaths.
Efficacy
Nineteen patients were evaluable for efficacy.
Five patients responded to treatment. Four patients with MDS had a marrow complete response, and 1 with tAML had a marrow partial response. Two of the patients with marrow complete response also had hematologic improvements.
Five patients had stable disease, 3 with MDS and 2 with tAML.
The median OS was 15.7 months for responders and 2.0 months for non-responders (P=0.0070). The median OS was 12.0 months for MDS patients and 2.0 months for tAML patients (P<0.0001).
“The publication of results from this historical study provides support of the relationship between bone marrow blast response and improvement in overall survival in this group of patients with MDS and acute myeloid leukemia for whom no FDA-approved treatments are currently available,” said Ramesh Kumar, president and chief executive officer of Onconova Therapeutics, Inc.
He added that these data are “fundamental to the rationale” of ongoing studies of rigosertib in high-risk MDS patients.
Drug can treat severely ill SCD patients, case suggests
ATLANTA—Results of a case study suggest voxelotor (previously GBT440) can be effective in severely ill patients with sickle cell disease (SCD).
Voxelotor is currently under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older.
A 67-year-old male SCD patient could not participate in the study due to severe, transfusion-refractory anemia, so he received voxelotor via compassionate access.
This patient’s results were presented at the Sickle Cell Disease Association of America (SCDAA) 45th Annual National Convention.
The patient had the HbSS genotype with severe anemia that was refractory to transfusion. The patient had developed red cell antibodies after receiving multiple transfusions, and these antibodies prevented further transfusions to correct his anemia.
The patient also had moderate chronic obstructive pulmonary disease requiring supplemental oxygen therapy, recurrent and frequent pain exacerbations, extreme fatigue, and clinical depression.
The patient received voxelotor at 900 mg orally once daily. He responded to the treatment within 1 to 2 weeks, experiencing improvements in pain, fatigue, and overall mental health (as measured by the Patient Health Quality-9 score).
The patient’s hemoglobin levels rose quickly, to approximately 1.5 g/dL above baseline, with a sustained increase over 66 weeks in the range of 1 to 1.5 g/dL.
There were reductions in reticulocyte count and bilirubin as well, both consistent with diminished hemolysis.
The patient’s blood oxygen saturation improved on the standard walk test, from 86 mmHg at baseline to 96 mmHg at 65 weeks, and he discontinued continuous oxygen supplementation.
The patient has not been hospitalized due to sickle cell pain since he started taking voxelotor.
He has experienced a treatment-related side effect—grade 2 diarrhea. This occurred 9 weeks after he started voxelotor treatment, when the dose was increased to 1500 mg daily, but it resolved upon return to 900 mg. The patient has experienced no other treatment-related side effects.
Clinical and laboratory improvements have continued for more than 17 months, and the patient remains on treatment today under compassionate use access.
“This severely ill SCD patient’s clinical response, assessed by both objective and subjective measures, illustrates why we are encouraged by the voxelotor program,” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics, the company developing voxelotor.
“We plan to present additional data from other severely ill sickle cell patients who have received voxelotor via single-patient compassionate access treatment at FSCDR [the Foundation for Sickle Cell Disease Research] at an upcoming medical meeting. Of course, controlled clinical trials are needed to assess the efficacy and safety of voxelotor in SCD patients, including those with severe anemia.”
ATLANTA—Results of a case study suggest voxelotor (previously GBT440) can be effective in severely ill patients with sickle cell disease (SCD).
Voxelotor is currently under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older.
A 67-year-old male SCD patient could not participate in the study due to severe, transfusion-refractory anemia, so he received voxelotor via compassionate access.
This patient’s results were presented at the Sickle Cell Disease Association of America (SCDAA) 45th Annual National Convention.
The patient had the HbSS genotype with severe anemia that was refractory to transfusion. The patient had developed red cell antibodies after receiving multiple transfusions, and these antibodies prevented further transfusions to correct his anemia.
The patient also had moderate chronic obstructive pulmonary disease requiring supplemental oxygen therapy, recurrent and frequent pain exacerbations, extreme fatigue, and clinical depression.
The patient received voxelotor at 900 mg orally once daily. He responded to the treatment within 1 to 2 weeks, experiencing improvements in pain, fatigue, and overall mental health (as measured by the Patient Health Quality-9 score).
The patient’s hemoglobin levels rose quickly, to approximately 1.5 g/dL above baseline, with a sustained increase over 66 weeks in the range of 1 to 1.5 g/dL.
There were reductions in reticulocyte count and bilirubin as well, both consistent with diminished hemolysis.
The patient’s blood oxygen saturation improved on the standard walk test, from 86 mmHg at baseline to 96 mmHg at 65 weeks, and he discontinued continuous oxygen supplementation.
The patient has not been hospitalized due to sickle cell pain since he started taking voxelotor.
He has experienced a treatment-related side effect—grade 2 diarrhea. This occurred 9 weeks after he started voxelotor treatment, when the dose was increased to 1500 mg daily, but it resolved upon return to 900 mg. The patient has experienced no other treatment-related side effects.
Clinical and laboratory improvements have continued for more than 17 months, and the patient remains on treatment today under compassionate use access.
“This severely ill SCD patient’s clinical response, assessed by both objective and subjective measures, illustrates why we are encouraged by the voxelotor program,” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics, the company developing voxelotor.
“We plan to present additional data from other severely ill sickle cell patients who have received voxelotor via single-patient compassionate access treatment at FSCDR [the Foundation for Sickle Cell Disease Research] at an upcoming medical meeting. Of course, controlled clinical trials are needed to assess the efficacy and safety of voxelotor in SCD patients, including those with severe anemia.”
ATLANTA—Results of a case study suggest voxelotor (previously GBT440) can be effective in severely ill patients with sickle cell disease (SCD).
Voxelotor is currently under investigation in the phase 3 HOPE study, which includes SCD patients age 12 and older.
A 67-year-old male SCD patient could not participate in the study due to severe, transfusion-refractory anemia, so he received voxelotor via compassionate access.
This patient’s results were presented at the Sickle Cell Disease Association of America (SCDAA) 45th Annual National Convention.
The patient had the HbSS genotype with severe anemia that was refractory to transfusion. The patient had developed red cell antibodies after receiving multiple transfusions, and these antibodies prevented further transfusions to correct his anemia.
The patient also had moderate chronic obstructive pulmonary disease requiring supplemental oxygen therapy, recurrent and frequent pain exacerbations, extreme fatigue, and clinical depression.
The patient received voxelotor at 900 mg orally once daily. He responded to the treatment within 1 to 2 weeks, experiencing improvements in pain, fatigue, and overall mental health (as measured by the Patient Health Quality-9 score).
The patient’s hemoglobin levels rose quickly, to approximately 1.5 g/dL above baseline, with a sustained increase over 66 weeks in the range of 1 to 1.5 g/dL.
There were reductions in reticulocyte count and bilirubin as well, both consistent with diminished hemolysis.
The patient’s blood oxygen saturation improved on the standard walk test, from 86 mmHg at baseline to 96 mmHg at 65 weeks, and he discontinued continuous oxygen supplementation.
The patient has not been hospitalized due to sickle cell pain since he started taking voxelotor.
He has experienced a treatment-related side effect—grade 2 diarrhea. This occurred 9 weeks after he started voxelotor treatment, when the dose was increased to 1500 mg daily, but it resolved upon return to 900 mg. The patient has experienced no other treatment-related side effects.
Clinical and laboratory improvements have continued for more than 17 months, and the patient remains on treatment today under compassionate use access.
“This severely ill SCD patient’s clinical response, assessed by both objective and subjective measures, illustrates why we are encouraged by the voxelotor program,” said Ted W. Love, MD, president and chief executive officer of Global Blood Therapeutics, the company developing voxelotor.
“We plan to present additional data from other severely ill sickle cell patients who have received voxelotor via single-patient compassionate access treatment at FSCDR [the Foundation for Sickle Cell Disease Research] at an upcoming medical meeting. Of course, controlled clinical trials are needed to assess the efficacy and safety of voxelotor in SCD patients, including those with severe anemia.”
FDA approves generic clofarabine
The US Food and Drug Administration (FDA) has approved Dr. Reddy’s Laboratories Ltd.’s Clofarabine Injection, a therapeutic equivalent generic version of Clolar® (clofarabine) Injection.
The generic drug is now approved to treat patients age 1 to 21 who have relapsed or refractory acute lymphoblastic leukemia and have received at least 2 prior treatment regimens.
Dr. Reddy’s Clofarabine Injection is available in single-dose, 20 mL flint vials containing 20 mg of clofarabine in 20 mL of solution (1 mg/mL).
The US Food and Drug Administration (FDA) has approved Dr. Reddy’s Laboratories Ltd.’s Clofarabine Injection, a therapeutic equivalent generic version of Clolar® (clofarabine) Injection.
The generic drug is now approved to treat patients age 1 to 21 who have relapsed or refractory acute lymphoblastic leukemia and have received at least 2 prior treatment regimens.
Dr. Reddy’s Clofarabine Injection is available in single-dose, 20 mL flint vials containing 20 mg of clofarabine in 20 mL of solution (1 mg/mL).
The US Food and Drug Administration (FDA) has approved Dr. Reddy’s Laboratories Ltd.’s Clofarabine Injection, a therapeutic equivalent generic version of Clolar® (clofarabine) Injection.
The generic drug is now approved to treat patients age 1 to 21 who have relapsed or refractory acute lymphoblastic leukemia and have received at least 2 prior treatment regimens.
Dr. Reddy’s Clofarabine Injection is available in single-dose, 20 mL flint vials containing 20 mg of clofarabine in 20 mL of solution (1 mg/mL).
Generic azacitidine approved in Canada
Health Canada has approved Dr. Reddy’s Laboratories Ltd.’s Azacitidine for Injection 100 mg/vial, a bioequivalent generic version of VIDAZA® (azacitidine for injection).
The generic drug is approved for the same indications as VIDAZA®.
This includes treating adults with intermediate-2 or high-risk myelodysplastic syndromes (according to the International Prognostic Scoring System) who are not eligible for hematopoietic stem cell transplant.
It also includes treating adults who have acute myeloid leukemia with 20% to 30% blasts and multi-lineage dysplasia (according to World Health Organization classification) who are not eligible for hematopoietic stem cell transplant.
“The approval and launch of Azacitidine for Injection is an important milestone for Dr. Reddy’s in Canada,” said Vinod Ramachandran, PhD, country manager, Dr. Reddy’s Canada.
“The launch of the first generic azacitidine for injection is another step in our long-term commitment to bring more cost-effective options to Canadian patients.”
Health Canada has approved Dr. Reddy’s Laboratories Ltd.’s Azacitidine for Injection 100 mg/vial, a bioequivalent generic version of VIDAZA® (azacitidine for injection).
The generic drug is approved for the same indications as VIDAZA®.
This includes treating adults with intermediate-2 or high-risk myelodysplastic syndromes (according to the International Prognostic Scoring System) who are not eligible for hematopoietic stem cell transplant.
It also includes treating adults who have acute myeloid leukemia with 20% to 30% blasts and multi-lineage dysplasia (according to World Health Organization classification) who are not eligible for hematopoietic stem cell transplant.
“The approval and launch of Azacitidine for Injection is an important milestone for Dr. Reddy’s in Canada,” said Vinod Ramachandran, PhD, country manager, Dr. Reddy’s Canada.
“The launch of the first generic azacitidine for injection is another step in our long-term commitment to bring more cost-effective options to Canadian patients.”
Health Canada has approved Dr. Reddy’s Laboratories Ltd.’s Azacitidine for Injection 100 mg/vial, a bioequivalent generic version of VIDAZA® (azacitidine for injection).
The generic drug is approved for the same indications as VIDAZA®.
This includes treating adults with intermediate-2 or high-risk myelodysplastic syndromes (according to the International Prognostic Scoring System) who are not eligible for hematopoietic stem cell transplant.
It also includes treating adults who have acute myeloid leukemia with 20% to 30% blasts and multi-lineage dysplasia (according to World Health Organization classification) who are not eligible for hematopoietic stem cell transplant.
“The approval and launch of Azacitidine for Injection is an important milestone for Dr. Reddy’s in Canada,” said Vinod Ramachandran, PhD, country manager, Dr. Reddy’s Canada.
“The launch of the first generic azacitidine for injection is another step in our long-term commitment to bring more cost-effective options to Canadian patients.”
Restrictive transfusion method safe in cardiac surgery patients
ANAHEIM, CA—Results of a large study suggest a restrictive transfusion strategy is safe for moderate- to high-risk patients undergoing cardiac surgery.
Researchers found that patients had similar rates of various outcomes—death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis—whether they received red blood cell (RBC) transfusions according to a restrictive strategy or a liberal one.
C. David Mazer, MD, of St. Michael’s Hospital in Toronto, Ontario, Canada, presented these results at the American Heart Association’s Scientific Sessions 2017.
Results were simultaneously published in NEJM.
Dr Mazer and his colleagues studied 5243 adults undergoing cardiac surgery. They all had a European System for Cardiac Operative Risk Evaluation I score of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery).
Patients were randomized to receive RBC transfusions according to a restrictive strategy or a liberal one.
With the restrictive strategy, patients received transfusions if their hemoglobin level was below 7.5 g/dL, starting from induction of anesthesia.
With the liberal strategy, patients were transfused if their hemoglobin level was less than 9.5 g/dL in the operating room or intensive care unit (ICU) or was less than 8.5 g/dL in the non-ICU ward.
Results
There were 4860 patients in the per-protocol analysis—2430 in each transfusion group. Baseline characteristics were similar between the groups.
The rate of RBC transfusion was 52.3% in the restrictive group and 72.6% in the liberal group. The odds ratio (OR) was 0.41 (95% confidence interval [CI], 0.37 to 0.47).
Transfused patients received a median of 2 RBC units (interquartile range [IQR], 1 to 4) in the restrictive group and 3 units (IQR, 2 to 5) in the liberal group.
The study’s primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first.
This outcome occurred in 11.4% of patients in the restrictive group and 12.5% of those in the liberal group. The absolute risk difference was −1.11 percentage points (95% CI, −2.93 to 0.72), and the odds ratio was 0.90 (95% CI, 0.76 to 1.07; P<0.001 for noninferiority).
There were no significant differences between the groups when it came to the individual components of the composite outcome.
“We have shown that this [restrictive] approach to transfusion is safe in moderate- to high-risk patients undergoing cardiac surgery,” Dr Mazer said.
“Such practices can also reduce the number of patients transfused, the amount of blood transfused, the impact on blood supply, and costs to the healthcare system.”
ANAHEIM, CA—Results of a large study suggest a restrictive transfusion strategy is safe for moderate- to high-risk patients undergoing cardiac surgery.
Researchers found that patients had similar rates of various outcomes—death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis—whether they received red blood cell (RBC) transfusions according to a restrictive strategy or a liberal one.
C. David Mazer, MD, of St. Michael’s Hospital in Toronto, Ontario, Canada, presented these results at the American Heart Association’s Scientific Sessions 2017.
Results were simultaneously published in NEJM.
Dr Mazer and his colleagues studied 5243 adults undergoing cardiac surgery. They all had a European System for Cardiac Operative Risk Evaluation I score of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery).
Patients were randomized to receive RBC transfusions according to a restrictive strategy or a liberal one.
With the restrictive strategy, patients received transfusions if their hemoglobin level was below 7.5 g/dL, starting from induction of anesthesia.
With the liberal strategy, patients were transfused if their hemoglobin level was less than 9.5 g/dL in the operating room or intensive care unit (ICU) or was less than 8.5 g/dL in the non-ICU ward.
Results
There were 4860 patients in the per-protocol analysis—2430 in each transfusion group. Baseline characteristics were similar between the groups.
The rate of RBC transfusion was 52.3% in the restrictive group and 72.6% in the liberal group. The odds ratio (OR) was 0.41 (95% confidence interval [CI], 0.37 to 0.47).
Transfused patients received a median of 2 RBC units (interquartile range [IQR], 1 to 4) in the restrictive group and 3 units (IQR, 2 to 5) in the liberal group.
The study’s primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first.
This outcome occurred in 11.4% of patients in the restrictive group and 12.5% of those in the liberal group. The absolute risk difference was −1.11 percentage points (95% CI, −2.93 to 0.72), and the odds ratio was 0.90 (95% CI, 0.76 to 1.07; P<0.001 for noninferiority).
There were no significant differences between the groups when it came to the individual components of the composite outcome.
“We have shown that this [restrictive] approach to transfusion is safe in moderate- to high-risk patients undergoing cardiac surgery,” Dr Mazer said.
“Such practices can also reduce the number of patients transfused, the amount of blood transfused, the impact on blood supply, and costs to the healthcare system.”
ANAHEIM, CA—Results of a large study suggest a restrictive transfusion strategy is safe for moderate- to high-risk patients undergoing cardiac surgery.
Researchers found that patients had similar rates of various outcomes—death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis—whether they received red blood cell (RBC) transfusions according to a restrictive strategy or a liberal one.
C. David Mazer, MD, of St. Michael’s Hospital in Toronto, Ontario, Canada, presented these results at the American Heart Association’s Scientific Sessions 2017.
Results were simultaneously published in NEJM.
Dr Mazer and his colleagues studied 5243 adults undergoing cardiac surgery. They all had a European System for Cardiac Operative Risk Evaluation I score of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery).
Patients were randomized to receive RBC transfusions according to a restrictive strategy or a liberal one.
With the restrictive strategy, patients received transfusions if their hemoglobin level was below 7.5 g/dL, starting from induction of anesthesia.
With the liberal strategy, patients were transfused if their hemoglobin level was less than 9.5 g/dL in the operating room or intensive care unit (ICU) or was less than 8.5 g/dL in the non-ICU ward.
Results
There were 4860 patients in the per-protocol analysis—2430 in each transfusion group. Baseline characteristics were similar between the groups.
The rate of RBC transfusion was 52.3% in the restrictive group and 72.6% in the liberal group. The odds ratio (OR) was 0.41 (95% confidence interval [CI], 0.37 to 0.47).
Transfused patients received a median of 2 RBC units (interquartile range [IQR], 1 to 4) in the restrictive group and 3 units (IQR, 2 to 5) in the liberal group.
The study’s primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first.
This outcome occurred in 11.4% of patients in the restrictive group and 12.5% of those in the liberal group. The absolute risk difference was −1.11 percentage points (95% CI, −2.93 to 0.72), and the odds ratio was 0.90 (95% CI, 0.76 to 1.07; P<0.001 for noninferiority).
There were no significant differences between the groups when it came to the individual components of the composite outcome.
“We have shown that this [restrictive] approach to transfusion is safe in moderate- to high-risk patients undergoing cardiac surgery,” Dr Mazer said.
“Such practices can also reduce the number of patients transfused, the amount of blood transfused, the impact on blood supply, and costs to the healthcare system.”
Antibody prevents GVHD in mice
Preclinical research suggests PRO 140, a humanized anti-CCR5 monoclonal antibody, can prevent graft-versus-host disease (GVHD) in mice.
Mice that received 2 mg of PRO 140 twice weekly showed no signs of GVHD throughout the study period.
On the other hand, all control mice exhibited signs of GVHD, starting 25 days after engraftment, and had to be sacrificed early.
Researchers reported these results in Biology of Blood and Marrow Transplantation.
The study’s lead author, Denis R. Burger, PhD, is chief science officer of CytoDyn, the company developing PRO 140.
PRO 140 targets the CCR5 receptor, a molecule that modulates the immune cell trafficking crucial for the development of acute GVHD.
Previous clinical studies have shown that inhibiting CCR5 can reduce the clinical impact of acute GVHD without significantly affecting the engraftment of transplanted hematopoietic stem cells (HSCs).
This new study supports the idea that the CCR5 receptor on engrafted cells is critical for the development of acute GVHD and that preventing this receptor from recognizing certain immune signaling molecules is a viable approach to mitigating acute GVHD.
Dr Burger and his colleagues tested PRO 140 in NOD-scid IL-2Rynull mice transplanted with human HSCs.
Mice received 2 different doses of PRO 140 or a control antibody—2 mg or 0.2 mg—twice weekly and were followed for a maximum of 75 days.
Engraftment at the higher dose
Mice that received the 2 mg dose of PRO 140 or the control antibody had received HSCs from a 56-year-old donor.
Engraftment was similar between control and PRO 140-treated mice for the first 30+ days. However, at day 50, there were significantly fewer human CD45+ cells in the PRO 140-treated mice (P=0.034).
At 54 days, control mice had greater engraftment of mature T cells than treated mice in the peripheral blood (63.2% vs 49.8%) and bone marrow (40.2% vs 26.4%).
GVHD at the higher dose
Throughout the study period, there were no physical signs of GVHD in the PRO 140-treated mice.
However, control mice exhibited signs of GVHD starting at day 25 after bone marrow engraftment. Signs included ruffled fur, lethargy, hunching, and weight loss.
There was a significant difference in survival between the 2 groups (P<0.01). All of the control mice had to be sacrificed early, by day 56, whereas all of the PRO 140-treated animals were alive until planned sacrifice at day 75.
Engraftment at the low dose
Mice that received the 0.2 mg dose of PRO 140 or the control antibody had received HSCs from a 26-year-old donor.
Mice in the treatment and control groups achieved the same percentage of CD45+ engraftment. However, PRO 140-treated mice achieved engraftment about 20 days later than control mice (P<0.01).
GVHD at the low dose
Both control and PRO 140-treated mice showed signs of GVHD. However, weight loss was significantly greater among control mice (P<0.05).
Survival was significantly worse among control mice as well (P<0.05). All control mice were dead by 31 days, and all PRO 140-treated mice were dead by 54 days.
The researchers said the difference in survival times between these mice and the mice treated with the higher dose of antibody suggest the younger HSC donor produced more aggressive GVHD.
“This research provided CytoDyn with strong rationale for exploring the use of PRO 140 in . . . the prevention of GVHD,” Dr Burger said.
“The potential of PRO 140 to prevent this life-threatening condition could help extend the use of [HSC] transplantation, an important and effective therapy, to more patients.”
CytoDyn is currently enrolling patients in a phase 2 trial of PRO 140 in leukemia patients undergoing transplant.
Preclinical research suggests PRO 140, a humanized anti-CCR5 monoclonal antibody, can prevent graft-versus-host disease (GVHD) in mice.
Mice that received 2 mg of PRO 140 twice weekly showed no signs of GVHD throughout the study period.
On the other hand, all control mice exhibited signs of GVHD, starting 25 days after engraftment, and had to be sacrificed early.
Researchers reported these results in Biology of Blood and Marrow Transplantation.
The study’s lead author, Denis R. Burger, PhD, is chief science officer of CytoDyn, the company developing PRO 140.
PRO 140 targets the CCR5 receptor, a molecule that modulates the immune cell trafficking crucial for the development of acute GVHD.
Previous clinical studies have shown that inhibiting CCR5 can reduce the clinical impact of acute GVHD without significantly affecting the engraftment of transplanted hematopoietic stem cells (HSCs).
This new study supports the idea that the CCR5 receptor on engrafted cells is critical for the development of acute GVHD and that preventing this receptor from recognizing certain immune signaling molecules is a viable approach to mitigating acute GVHD.
Dr Burger and his colleagues tested PRO 140 in NOD-scid IL-2Rynull mice transplanted with human HSCs.
Mice received 2 different doses of PRO 140 or a control antibody—2 mg or 0.2 mg—twice weekly and were followed for a maximum of 75 days.
Engraftment at the higher dose
Mice that received the 2 mg dose of PRO 140 or the control antibody had received HSCs from a 56-year-old donor.
Engraftment was similar between control and PRO 140-treated mice for the first 30+ days. However, at day 50, there were significantly fewer human CD45+ cells in the PRO 140-treated mice (P=0.034).
At 54 days, control mice had greater engraftment of mature T cells than treated mice in the peripheral blood (63.2% vs 49.8%) and bone marrow (40.2% vs 26.4%).
GVHD at the higher dose
Throughout the study period, there were no physical signs of GVHD in the PRO 140-treated mice.
However, control mice exhibited signs of GVHD starting at day 25 after bone marrow engraftment. Signs included ruffled fur, lethargy, hunching, and weight loss.
There was a significant difference in survival between the 2 groups (P<0.01). All of the control mice had to be sacrificed early, by day 56, whereas all of the PRO 140-treated animals were alive until planned sacrifice at day 75.
Engraftment at the low dose
Mice that received the 0.2 mg dose of PRO 140 or the control antibody had received HSCs from a 26-year-old donor.
Mice in the treatment and control groups achieved the same percentage of CD45+ engraftment. However, PRO 140-treated mice achieved engraftment about 20 days later than control mice (P<0.01).
GVHD at the low dose
Both control and PRO 140-treated mice showed signs of GVHD. However, weight loss was significantly greater among control mice (P<0.05).
Survival was significantly worse among control mice as well (P<0.05). All control mice were dead by 31 days, and all PRO 140-treated mice were dead by 54 days.
The researchers said the difference in survival times between these mice and the mice treated with the higher dose of antibody suggest the younger HSC donor produced more aggressive GVHD.
“This research provided CytoDyn with strong rationale for exploring the use of PRO 140 in . . . the prevention of GVHD,” Dr Burger said.
“The potential of PRO 140 to prevent this life-threatening condition could help extend the use of [HSC] transplantation, an important and effective therapy, to more patients.”
CytoDyn is currently enrolling patients in a phase 2 trial of PRO 140 in leukemia patients undergoing transplant.
Preclinical research suggests PRO 140, a humanized anti-CCR5 monoclonal antibody, can prevent graft-versus-host disease (GVHD) in mice.
Mice that received 2 mg of PRO 140 twice weekly showed no signs of GVHD throughout the study period.
On the other hand, all control mice exhibited signs of GVHD, starting 25 days after engraftment, and had to be sacrificed early.
Researchers reported these results in Biology of Blood and Marrow Transplantation.
The study’s lead author, Denis R. Burger, PhD, is chief science officer of CytoDyn, the company developing PRO 140.
PRO 140 targets the CCR5 receptor, a molecule that modulates the immune cell trafficking crucial for the development of acute GVHD.
Previous clinical studies have shown that inhibiting CCR5 can reduce the clinical impact of acute GVHD without significantly affecting the engraftment of transplanted hematopoietic stem cells (HSCs).
This new study supports the idea that the CCR5 receptor on engrafted cells is critical for the development of acute GVHD and that preventing this receptor from recognizing certain immune signaling molecules is a viable approach to mitigating acute GVHD.
Dr Burger and his colleagues tested PRO 140 in NOD-scid IL-2Rynull mice transplanted with human HSCs.
Mice received 2 different doses of PRO 140 or a control antibody—2 mg or 0.2 mg—twice weekly and were followed for a maximum of 75 days.
Engraftment at the higher dose
Mice that received the 2 mg dose of PRO 140 or the control antibody had received HSCs from a 56-year-old donor.
Engraftment was similar between control and PRO 140-treated mice for the first 30+ days. However, at day 50, there were significantly fewer human CD45+ cells in the PRO 140-treated mice (P=0.034).
At 54 days, control mice had greater engraftment of mature T cells than treated mice in the peripheral blood (63.2% vs 49.8%) and bone marrow (40.2% vs 26.4%).
GVHD at the higher dose
Throughout the study period, there were no physical signs of GVHD in the PRO 140-treated mice.
However, control mice exhibited signs of GVHD starting at day 25 after bone marrow engraftment. Signs included ruffled fur, lethargy, hunching, and weight loss.
There was a significant difference in survival between the 2 groups (P<0.01). All of the control mice had to be sacrificed early, by day 56, whereas all of the PRO 140-treated animals were alive until planned sacrifice at day 75.
Engraftment at the low dose
Mice that received the 0.2 mg dose of PRO 140 or the control antibody had received HSCs from a 26-year-old donor.
Mice in the treatment and control groups achieved the same percentage of CD45+ engraftment. However, PRO 140-treated mice achieved engraftment about 20 days later than control mice (P<0.01).
GVHD at the low dose
Both control and PRO 140-treated mice showed signs of GVHD. However, weight loss was significantly greater among control mice (P<0.05).
Survival was significantly worse among control mice as well (P<0.05). All control mice were dead by 31 days, and all PRO 140-treated mice were dead by 54 days.
The researchers said the difference in survival times between these mice and the mice treated with the higher dose of antibody suggest the younger HSC donor produced more aggressive GVHD.
“This research provided CytoDyn with strong rationale for exploring the use of PRO 140 in . . . the prevention of GVHD,” Dr Burger said.
“The potential of PRO 140 to prevent this life-threatening condition could help extend the use of [HSC] transplantation, an important and effective therapy, to more patients.”
CytoDyn is currently enrolling patients in a phase 2 trial of PRO 140 in leukemia patients undergoing transplant.
Parity laws don’t lower oral cancer drug costs for everyone
US state laws intended to ensure fair prices for oral cancer drugs have had a mixed impact on patients’ pocketbooks, according to a study published in JAMA Oncology.
A total of 43 states and Washington, DC, have enacted parity laws, which require that patients pay no more for an oral cancer treatment than they would for an infusion of the same treatment.
Researchers analyzed the impact of these laws and observed modest improvements in costs for some patients.
However, patients who were already paying the most for their medications saw their monthly costs go up.
“Although parity laws appear to help reduce out-of-pocket spending for some patients, they may not fully address affordability for patients needing cancer drugs,” said study author Stacie B. Dusetzina, PhD, of the University of North Carolina at Chapel Hill.
“We need to consider ways to address drug pricing directly and to improve benefit design to make sure that all patients can access prescribed drugs.”
To gauge the impact of parity laws on treatment costs, Dr Dusetzina and her colleagues analyzed health claims data for 63,780 adults from 3 large, nationwide insurance companies before and after the laws were enacted, from 2008 to 2012.
The team compared the cost of filling an oral cancer drug prescription for patients with health insurance plans that were covered by the state laws (fully insured) and patients whose plans were not (self-funded). All patients lived in 1 of 16 states that had passed parity laws at the time of the study.
About half of patients (51.4%) had fully insured plans, and the other half (48.6%) had self-funded plans.
For the entire cohort, the use of oral cancer drugs increased from 18% in the months before parity laws were passed to 22% in the months after (adjusted difference-in-differences risk ratio [aDDRR], 1.04; 95% confidence interval [CI], 0.96-1.13; P=0.34).
The proportion of prescription fills for oral drugs without copayment increased from 15.0% to 53.0% for patients with fully insured plans and from 12.3% to 18.0% in patients with self-funded plans (aDDRR, 2.36; 95% CI, 2.00-2.79; P<0.001).
“From our results, it looks like many plans decided they would just set the co-pay for oral drugs to $0,” Dr Dusetzina said. “Instead of $30 per month, those fills were now $0.”
The proportion of prescription fills with out-of-pocket cost of more than $100 per month increased from 8.4% to 11.1% for patients with fully insured plans but decreased from 12.0% to 11.7% for those with self-funded plans (aDDRR, 1.36; 95% CI, 1.11-1.68; P=0.004).
Patients paying the most for their oral cancer drug prescriptions experienced increases in their monthly out-of-pocket costs after parity laws were passed.
For patients whose costs were more expensive than 95% of other patients, their out-of-pocket costs increased an estimated $143.25 per month. Those paying more than 90% of what other patients paid saw their costs increase by $37.19 per month.
“One of the biggest problems with parity laws as they are written is that they don’t address the prices of these medications, which can be very high,” Dr Dusetzina noted.
“Parity can be reached as long as the coverage is the same for both oral and infused cancer therapies. Because we’re now seeing more people insured by plans with high deductibles or plans that require them to pay a percentage of their drug costs, parity may not reduce spending for some patients.”
However, Dr Dusetzina and her colleagues did find that patients who paid the least for their oral cancer treatments saw their estimated monthly out-of-pocket spending decrease.
Patients in the 25th percentile saw an estimated decrease of $19.44 per month, those in the 50th percentile saw a $32.13 decrease, and patients in the 75th percentile saw a decrease of $10.83.
On the other hand, the researchers also found that average 6-month healthcare costs—including what was paid by insurance companies and patients—did not change significantly as a result of parity laws.
The aDDRR was 0.96 (95% CI, 0.90-1.02; P=0.09) for all cancer treatments and 1.06 (95% CI, 0.93-1.20; P=0.40) for oral cancer drugs.
“One of the key arguments against passing parity, both for states that haven’t passed it and for legislation at the federal level, has been that it may increase costs to health plans,” Dr Dusetzina said. “But we didn’t find evidence of that.”
US state laws intended to ensure fair prices for oral cancer drugs have had a mixed impact on patients’ pocketbooks, according to a study published in JAMA Oncology.
A total of 43 states and Washington, DC, have enacted parity laws, which require that patients pay no more for an oral cancer treatment than they would for an infusion of the same treatment.
Researchers analyzed the impact of these laws and observed modest improvements in costs for some patients.
However, patients who were already paying the most for their medications saw their monthly costs go up.
“Although parity laws appear to help reduce out-of-pocket spending for some patients, they may not fully address affordability for patients needing cancer drugs,” said study author Stacie B. Dusetzina, PhD, of the University of North Carolina at Chapel Hill.
“We need to consider ways to address drug pricing directly and to improve benefit design to make sure that all patients can access prescribed drugs.”
To gauge the impact of parity laws on treatment costs, Dr Dusetzina and her colleagues analyzed health claims data for 63,780 adults from 3 large, nationwide insurance companies before and after the laws were enacted, from 2008 to 2012.
The team compared the cost of filling an oral cancer drug prescription for patients with health insurance plans that were covered by the state laws (fully insured) and patients whose plans were not (self-funded). All patients lived in 1 of 16 states that had passed parity laws at the time of the study.
About half of patients (51.4%) had fully insured plans, and the other half (48.6%) had self-funded plans.
For the entire cohort, the use of oral cancer drugs increased from 18% in the months before parity laws were passed to 22% in the months after (adjusted difference-in-differences risk ratio [aDDRR], 1.04; 95% confidence interval [CI], 0.96-1.13; P=0.34).
The proportion of prescription fills for oral drugs without copayment increased from 15.0% to 53.0% for patients with fully insured plans and from 12.3% to 18.0% in patients with self-funded plans (aDDRR, 2.36; 95% CI, 2.00-2.79; P<0.001).
“From our results, it looks like many plans decided they would just set the co-pay for oral drugs to $0,” Dr Dusetzina said. “Instead of $30 per month, those fills were now $0.”
The proportion of prescription fills with out-of-pocket cost of more than $100 per month increased from 8.4% to 11.1% for patients with fully insured plans but decreased from 12.0% to 11.7% for those with self-funded plans (aDDRR, 1.36; 95% CI, 1.11-1.68; P=0.004).
Patients paying the most for their oral cancer drug prescriptions experienced increases in their monthly out-of-pocket costs after parity laws were passed.
For patients whose costs were more expensive than 95% of other patients, their out-of-pocket costs increased an estimated $143.25 per month. Those paying more than 90% of what other patients paid saw their costs increase by $37.19 per month.
“One of the biggest problems with parity laws as they are written is that they don’t address the prices of these medications, which can be very high,” Dr Dusetzina noted.
“Parity can be reached as long as the coverage is the same for both oral and infused cancer therapies. Because we’re now seeing more people insured by plans with high deductibles or plans that require them to pay a percentage of their drug costs, parity may not reduce spending for some patients.”
However, Dr Dusetzina and her colleagues did find that patients who paid the least for their oral cancer treatments saw their estimated monthly out-of-pocket spending decrease.
Patients in the 25th percentile saw an estimated decrease of $19.44 per month, those in the 50th percentile saw a $32.13 decrease, and patients in the 75th percentile saw a decrease of $10.83.
On the other hand, the researchers also found that average 6-month healthcare costs—including what was paid by insurance companies and patients—did not change significantly as a result of parity laws.
The aDDRR was 0.96 (95% CI, 0.90-1.02; P=0.09) for all cancer treatments and 1.06 (95% CI, 0.93-1.20; P=0.40) for oral cancer drugs.
“One of the key arguments against passing parity, both for states that haven’t passed it and for legislation at the federal level, has been that it may increase costs to health plans,” Dr Dusetzina said. “But we didn’t find evidence of that.”
US state laws intended to ensure fair prices for oral cancer drugs have had a mixed impact on patients’ pocketbooks, according to a study published in JAMA Oncology.
A total of 43 states and Washington, DC, have enacted parity laws, which require that patients pay no more for an oral cancer treatment than they would for an infusion of the same treatment.
Researchers analyzed the impact of these laws and observed modest improvements in costs for some patients.
However, patients who were already paying the most for their medications saw their monthly costs go up.
“Although parity laws appear to help reduce out-of-pocket spending for some patients, they may not fully address affordability for patients needing cancer drugs,” said study author Stacie B. Dusetzina, PhD, of the University of North Carolina at Chapel Hill.
“We need to consider ways to address drug pricing directly and to improve benefit design to make sure that all patients can access prescribed drugs.”
To gauge the impact of parity laws on treatment costs, Dr Dusetzina and her colleagues analyzed health claims data for 63,780 adults from 3 large, nationwide insurance companies before and after the laws were enacted, from 2008 to 2012.
The team compared the cost of filling an oral cancer drug prescription for patients with health insurance plans that were covered by the state laws (fully insured) and patients whose plans were not (self-funded). All patients lived in 1 of 16 states that had passed parity laws at the time of the study.
About half of patients (51.4%) had fully insured plans, and the other half (48.6%) had self-funded plans.
For the entire cohort, the use of oral cancer drugs increased from 18% in the months before parity laws were passed to 22% in the months after (adjusted difference-in-differences risk ratio [aDDRR], 1.04; 95% confidence interval [CI], 0.96-1.13; P=0.34).
The proportion of prescription fills for oral drugs without copayment increased from 15.0% to 53.0% for patients with fully insured plans and from 12.3% to 18.0% in patients with self-funded plans (aDDRR, 2.36; 95% CI, 2.00-2.79; P<0.001).
“From our results, it looks like many plans decided they would just set the co-pay for oral drugs to $0,” Dr Dusetzina said. “Instead of $30 per month, those fills were now $0.”
The proportion of prescription fills with out-of-pocket cost of more than $100 per month increased from 8.4% to 11.1% for patients with fully insured plans but decreased from 12.0% to 11.7% for those with self-funded plans (aDDRR, 1.36; 95% CI, 1.11-1.68; P=0.004).
Patients paying the most for their oral cancer drug prescriptions experienced increases in their monthly out-of-pocket costs after parity laws were passed.
For patients whose costs were more expensive than 95% of other patients, their out-of-pocket costs increased an estimated $143.25 per month. Those paying more than 90% of what other patients paid saw their costs increase by $37.19 per month.
“One of the biggest problems with parity laws as they are written is that they don’t address the prices of these medications, which can be very high,” Dr Dusetzina noted.
“Parity can be reached as long as the coverage is the same for both oral and infused cancer therapies. Because we’re now seeing more people insured by plans with high deductibles or plans that require them to pay a percentage of their drug costs, parity may not reduce spending for some patients.”
However, Dr Dusetzina and her colleagues did find that patients who paid the least for their oral cancer treatments saw their estimated monthly out-of-pocket spending decrease.
Patients in the 25th percentile saw an estimated decrease of $19.44 per month, those in the 50th percentile saw a $32.13 decrease, and patients in the 75th percentile saw a decrease of $10.83.
On the other hand, the researchers also found that average 6-month healthcare costs—including what was paid by insurance companies and patients—did not change significantly as a result of parity laws.
The aDDRR was 0.96 (95% CI, 0.90-1.02; P=0.09) for all cancer treatments and 1.06 (95% CI, 0.93-1.20; P=0.40) for oral cancer drugs.
“One of the key arguments against passing parity, both for states that haven’t passed it and for legislation at the federal level, has been that it may increase costs to health plans,” Dr Dusetzina said. “But we didn’t find evidence of that.”
TV time linked to VTE risk, even among active viewers
ANAHEIM, CA—New research suggests a person’s risk of developing venous thromboembolism (VTE) increases with the amount of time he or she spends watching television, even if that person is physically active.
Study participants who reported watching TV “very often” were more likely to develop VTE than those who reported watching TV “never or seldom,” and this was true even among subjects who met a recommended level of physical activity.
Mary Cushman, MD, of the Larner College of Medicine at the University of Vermont in Burlington, and her colleagues presented these findings in a poster at the American Heart Association’s Scientific Sessions 2017 (presentation S5169).
The researchers analyzed 15,158 middle-aged (45-64 years) subjects participating in the Atherosclerosis Risk in Communities Study.
TV viewing habits and other information on these individuals was collected in 1987-1989, 1993-1995, and 2009-2011.
The researchers used a Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident VTE according to subjects’ frequency of TV viewing.
Options for TV viewing included “never or seldom,” “sometimes,” “often,” or “very often.”
The researchers identified 691 VTEs during the 299,767 person-years of follow-up.
A multivariable analysis revealed an increased risk of VTE with increased TV viewing. The HR was 1.71 (95% CI: 1.26-2.32; P for trend=0.036) for subjects who reported watching TV “very often,” compared to subjects who watched TV “never or seldom.”
Among subjects who met a recommended level of physical activity, the HR was 1.80 (95% CI: 1.04-3.09) for those who watched TV “very often,” compared to those who watched TV “never or seldom.”
The researchers noted that obesity was more common in subjects who watched more TV. However, only about 25% (95% CI: 10.7-27.5) of the increased VTE risk could be explained by the presence of obesity.
“Watching TV itself isn’t likely bad, but we tend to snack and sit still for prolonged periods while watching,” Dr Cushman noted.
“Health professionals should take the time to ask patients about their fitness and sedentary time, such as prolonged sitting watching TV or at a computer.”
ANAHEIM, CA—New research suggests a person’s risk of developing venous thromboembolism (VTE) increases with the amount of time he or she spends watching television, even if that person is physically active.
Study participants who reported watching TV “very often” were more likely to develop VTE than those who reported watching TV “never or seldom,” and this was true even among subjects who met a recommended level of physical activity.
Mary Cushman, MD, of the Larner College of Medicine at the University of Vermont in Burlington, and her colleagues presented these findings in a poster at the American Heart Association’s Scientific Sessions 2017 (presentation S5169).
The researchers analyzed 15,158 middle-aged (45-64 years) subjects participating in the Atherosclerosis Risk in Communities Study.
TV viewing habits and other information on these individuals was collected in 1987-1989, 1993-1995, and 2009-2011.
The researchers used a Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident VTE according to subjects’ frequency of TV viewing.
Options for TV viewing included “never or seldom,” “sometimes,” “often,” or “very often.”
The researchers identified 691 VTEs during the 299,767 person-years of follow-up.
A multivariable analysis revealed an increased risk of VTE with increased TV viewing. The HR was 1.71 (95% CI: 1.26-2.32; P for trend=0.036) for subjects who reported watching TV “very often,” compared to subjects who watched TV “never or seldom.”
Among subjects who met a recommended level of physical activity, the HR was 1.80 (95% CI: 1.04-3.09) for those who watched TV “very often,” compared to those who watched TV “never or seldom.”
The researchers noted that obesity was more common in subjects who watched more TV. However, only about 25% (95% CI: 10.7-27.5) of the increased VTE risk could be explained by the presence of obesity.
“Watching TV itself isn’t likely bad, but we tend to snack and sit still for prolonged periods while watching,” Dr Cushman noted.
“Health professionals should take the time to ask patients about their fitness and sedentary time, such as prolonged sitting watching TV or at a computer.”
ANAHEIM, CA—New research suggests a person’s risk of developing venous thromboembolism (VTE) increases with the amount of time he or she spends watching television, even if that person is physically active.
Study participants who reported watching TV “very often” were more likely to develop VTE than those who reported watching TV “never or seldom,” and this was true even among subjects who met a recommended level of physical activity.
Mary Cushman, MD, of the Larner College of Medicine at the University of Vermont in Burlington, and her colleagues presented these findings in a poster at the American Heart Association’s Scientific Sessions 2017 (presentation S5169).
The researchers analyzed 15,158 middle-aged (45-64 years) subjects participating in the Atherosclerosis Risk in Communities Study.
TV viewing habits and other information on these individuals was collected in 1987-1989, 1993-1995, and 2009-2011.
The researchers used a Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident VTE according to subjects’ frequency of TV viewing.
Options for TV viewing included “never or seldom,” “sometimes,” “often,” or “very often.”
The researchers identified 691 VTEs during the 299,767 person-years of follow-up.
A multivariable analysis revealed an increased risk of VTE with increased TV viewing. The HR was 1.71 (95% CI: 1.26-2.32; P for trend=0.036) for subjects who reported watching TV “very often,” compared to subjects who watched TV “never or seldom.”
Among subjects who met a recommended level of physical activity, the HR was 1.80 (95% CI: 1.04-3.09) for those who watched TV “very often,” compared to those who watched TV “never or seldom.”
The researchers noted that obesity was more common in subjects who watched more TV. However, only about 25% (95% CI: 10.7-27.5) of the increased VTE risk could be explained by the presence of obesity.
“Watching TV itself isn’t likely bad, but we tend to snack and sit still for prolonged periods while watching,” Dr Cushman noted.
“Health professionals should take the time to ask patients about their fitness and sedentary time, such as prolonged sitting watching TV or at a computer.”